The present invention relates to sustained release pharmaceutical compositions containing one or more antibiotics. The invention is also directed to the use of such compositions to sterilize the tissues in the area of surgery (i.e., the "surgical field" or "field of surgery") prior to a surgical procedure and to prevent post-surgical infections.
Ophthalmic surgical procedures currently involve the topical application of betadine solution to the eyelid and other tissues adjacent to the eye prior to surgery. The preoperative procedures may also include topical instillation of argyrol to facilitate removal of mucus and other debris present on the cornea and conjunctiva. However, the foregoing procedures do not result in sterilization of the ophthalmic tissues which form the site of the surgery (e.g., the cornea, sclera or various other ophthalmic tissues).
Antimicrobial agents such as the aminoglycosides, penicillins and cephalosporins, being relatively insoluble in lipids, penetrate the eye poorly after systemic administration. Therefore, the surgical field is currently sterilized by subconjunctival injection of any one of various antibiotics. The most commonly used drug in subconjunctival injection is gentamicin (about 30 mg per injection). This method involves the insertion of a 20-gauge needle into the subconjunctival space, taking care not to pierce the conjunctiva; 0.1 ml to 1.0 ml of antibiotic is injected. This technique permits significant antibiotic to enter the corneoscleral limbus near the subconjunctival injection site. However, such injections present a significant risk of injury to ophthalmic tissues if performed improperly. Even when proper procedures are followed, such injections are painful and inherently involve at least some undesirable trauma due to the passing of the hypodermic needle through very delicate ophthalmic tissues. In addition, subconjunctival injections of antibiotics can result in nonuniform concentrations of the antibiotics in the cornea, and the concentrations attained may be inadequate. For example, the maximum gentamicin concentration attained in the aqueous humor of rabbits from subconjunctival injection is 8.8 ug/g. Although a concentration of 8.8 ug/g would be effective against some bacteria, a significantly higher concentration is required for more resistant strains. Still another problem is the fairly recent development of bacterial resistance to aminoglycoside antibiotics.
The intravenous ("IV") and oral dosage of quinolones have been suggested for prophylactic usage and as an alternative to subconjunctival injections. However, the maximum aqueous humor concentration from IV injection (200 mg) and oral dosage (1 g) of ciprofloxacin in humans is 0.16 ug/ml and 0.33 ug/ml, respectively, at one hour after administration. This is less than its MIC90 (0.5 ug/g). These non-ocular delivery routes are also associated with higher risks of systemic side effects. The topical application of existing antibiotic formulations is useful in cases of superficial infections, but is inadequate for the delivery of high concentrations of antibiotics to deeper eye tissues prior to surgery.
This risk of infection subsequent to ophthalmic surgery is a significant concern. The post-surgical application of an antibiotic is therefore normally desirable. However, as with the current procedures for sterilizing the ophthalmic field prior to surgery, the post-surgical administration of antibiotics by means of hypodermic injections has significant drawbacks.
Accordingly, improved methods of sterilizing ophthalmic tissues prior to surgery and preventing post surgical infections are needed.